BACKGROUND Drug efficacy against kelch 13 mutant malaria parasites can be determined in vitro with the ring-stage survival assay (RSA). The conventional assay protocol reflects the exposure profile of dihydroartemisinin. METHODS Taking into account that other anti-malarial peroxides, such as the synthetic ozonides OZ439 (artefenomel) and OZ609, have different pharmacokinetics, the RSA was adjusted to the concentration-time profile of these ozonides in humans and a novel, semi-automated readout was introduced. RESULTS When tested at clinically relevant parameters, it was shown that OZ439 and OZ609 are active against the Plasmodium falciparum clinical isolate Cam3.IR539T. CONCLUSION If the in vitro RSA does indeed predict the potency of compounds against parasites with increased tolerance to artemisinin and its derivatives, then the herein presented data suggest that following drug-pulses of at least 48 h, OZ439 and OZ609 will be highly potent against kelch 13 mutant isolates, such as P. falciparum Cam3.IR539T.

中文翻译：

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在新型环阶段存活试验中，在临床相关化合物的暴露参数下测试了抗疟原虫OZ439和OZ609。

背景技术可以通过环期存活测定法（RSA）在体外确定针对海藻13突变型疟疾寄生虫的药物功效。常规测定方案反映了双氢青蒿素的暴露情况。方法考虑到其他抗疟疾过氧化物，例如合成的臭氧化物OZ439（artefenomel）和OZ609具有不同的药代动力学，因此将RSA调整为这些臭氧化物在人体内的浓度-时间曲线，并实现了新型的半自动读数被介绍了。结果在临床相关参数上进行测试时，表明OZ439和OZ609对恶性疟原虫临床分离株Cam3.IR539T具有活性。结论如果体外RSA确实能预测化合物对青蒿素及其衍生物具有更高耐受性的寄生虫的效力，